AASLD: Oral HCV Combo Yields Rapid Response

Action Points

Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Explain that 10 patients with chronic hepatitis C virus (HCV) infection unresponsive to interferon/ribavirin therapy had undetectable HCV RNA 24 weeks after the end of treatment with two oral antiviral drugs active against HCV.

Point out that the treatment regimen had two antivirals with different mechanisms of action against HCV, and did not include interferon.

SAN FRANCISCO -- A combination of two investigational antiviral drugs with different mechanisms of action against hepatitis C virus (HCV) yielded quick and persistent responses in previous nonresponders without the use of pegylated interferon, a researcher said here.

By week eight of treatment -- and at every measurement thereafter -- HCV was undetectable in all nine patients who completed treatment in the phase 2b study, according to Kazuaki Chayama, MD, PhD, of Hiroshima University in Hiroshima, Japan.

A tenth patient, who stopped treatment at week two with high bilirubin levels and a detectable viral load, also had undetectable virus at week four but wasn't counted as a responder, Chayama said at the annual meeting of the American Association for the Study of Liver Diseases.

Nonetheless, he noted, the patient -- a 60-year-old woman -- still did not have detectable virus 24 weeks after she would have finished treatment.

He argued that the findings show that "high cure rates are possible" with the oral drug combination -- a replication complex inhibitor dubbed daclatasvir and a protease inhibitor called asunaprevir.

While the study was small, that's not necessarily a major issue, according to Norah Terrault, MD, of the University of California San Francisco, who was not part of the study but who was one of the moderators of the late-breaker session at which it was presented.

"I think that's valid at this stage," she said, "establishing for us that we don't have to have an interferon backbone."

Chayama and colleagues enrolled 10 patients with genotype 1b virus who had not responded to peginterferon and ribavirin -- the standard therapy until the approval earlier this year of two protease inhibitors that act directly on the virus.

Several others in the class (including asunaprevir) are being developed, as well as some in other classes, including those that block the action of some of the structural proteins of hepatitis C, such as daclatasvir.

Patients were treated with 60 milligrams daily of daclatasvir and initially 600 milligrams twice a day of asunaprevir. The latter dose was later reduced to 200 milligrams twice a day because of liver enzyme elevations discovered in a separate study.

They were treated for 24 weeks and followed for another 24, Chayama said.

Two serious adverse events were recorded: one was a case of grade three pyrexia, and the other was the 60-year-old woman who had hyperbilirubinemia -- thought to be at least partly related to the study drug -- which occurred during an attack of gastroenteritis that led to hospital admission.

Transient grade one liver enzyme elevations were seen in two patients, as well as a grade two elevation starting at week 16 of treatment, which resolved in the first two weeks after therapy ended.

Aside from those, seven patients reported grade one diarrhea, four reported grade one headache, and smaller numbers reported a scattering of other events, Chayama reported.

Although promising, the study still has some gaps, Terrault told MedPage Today. The combination has been tested only in patients with genotype 1b virus and only in a Japanese cohort, so it will need to be tested in a wider population, she said.

The study was supported by Bristol-Myers Squibb. Chayama reported financial links with the company, and several authors are employees of the company.

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